Deletion polymorphism in the α2B-adrenergic receptor gene is associated with flow-mediated dilatation of the brachial artery

A deletion variant of the α_2B-adrenergic receptor (α_2B-AR) has been associated with an increased risk of acute cardiac events in middle-aged men. Our aim was to determine the possible associations between the α_2B-AR gene deletion variant and indicators of subclinical atherosclerosis in the brachial and carotid arteries. A total of 148 middle-aged men participating in an epidemiological twin study on risk factors for subclinical coronary heart disease were genotyped using PCR. Flow-mediated dilatation (FMD) of the brachial artery, carotid artery compliance and carotid intima-media thickness were measured using high-resolution ultrasound. FMD was 6.2±5.0% in subjects with the I/I (insertion/insertion) genotype, 5.5±4.1% in the I/D (insertion/deletion) group and 4.1±3.8% in the D/D (deletion/deletion) group (P = 0.03 for trend). In multivariate regression analysis controlling for age, presence of hypertension, smoking, use of angiotensin-converting enzyme inhibitors and plasma levels of low-density lipoprotein cholesterol and lipoprotein (a), the association between the α_2B-AR genotype and FMD remained significant (P = 0.04 for trend). The α_2B-AR genotype was not associated with intima-media thickness or carotid artery compliance. These findings indicate that subjects homozygous for the deletion allele of α_2B-AR appear to have an increased risk of impaired endothelial function, which may provide an explanation for the previously observed increased risk of myocardial infarction in male subjects with this genotype. It is not known whether the association of the α_2B-AR polymorphism with endothelial function is direct, or is mediated via altered sympathetic activation.